Things came to a head there, but the roots of the parting of ways go much deeper, with October's 3-0 London derby defeat to West Ham being one of the disappointing results that ultimately undermined Villas-Boas' tenure.
In the Portuguese's place comes the management team of Tim Sherwood, Chris Ramsey and Les Ferdinand, as announced via TottenhamHotspur.com on Monday afternoon:
Media speculation—including this article by the Daily Telegraph's Matt Law—has Sherwood in with a chance of getting the job permanently.
Be it an audition for a full-time gig or just the first match of a caretaker spell, the immediate focus for Sherwood and his colleagues is to lead Spurs into the League Cup's semifinal stage and not to mention, record a morale-boosting win.
Predicting Spurs' starting lineup was tricky enough when Villas-Boas was in charge. As it was, the ex-manager's rotation of his resources never did quite lead to the discovery of what his best team was (or the closest thing to it).
With little idea of the caretaker management team's preferences when it comes to this squad, identifying who will play versus the Hammers will be more a case of guesswork than usual.
Definitely out in defence are the suspended Michael Dawson and the injured Jan Vertonghen. According to BBC Sport's match preview, though, Younes Kaboul could return, while SpursOfficial on Twitter confirmed Vlad Chiriches' possible inclusion.
Assuming the pair are fit enough to play, they would be a good bet to start together in central defence. Kyle Walker will likely carry on at right-back, while Danny Rose should be good to go at left-back with a week's full training under his belt (and 45 minutes in the Europa League last week).
Behind those four, Sherwood and his colleagues may opt to continue Brad Friedel's run in goal for the Capital One Cup. Hugo Lloris will want to play again as soon as possible after conceding five on Sunday, but with plenty of Premier League games coming up for him, a night off is not a bad idea.
Central midfield options are somewhat limited, with Paulinho suspended and the calf injury that caused Sandro to hobble off versus Liverpool keeping him out.
Mousa Dembele and Lewis Holtby should got the nod then, with the expectation that a much better performance is required versus Sam Allardyce's physical midfield than was seen versus the Reds.
The remaining positions are where things get interesting. Will the attack be part of the 4-2-3-1/4-3-3 that Villas-Boas preferred, or will something more akin to a 4-4-2 be on the agenda?
In part, it depends on what Sherwood has in mind for Emmanuel Adebayor (whose fitness status is not clear), Jermain Defoe and Roberto Soldado. An available Adebayor could be partnered with either of his fellow strikers in an attempt to re-energise Spurs' goal-shy forward line.
In the absence of news as to Adebayor's availability, it will be assumed that another direction will be taken. This one could feature Defoe up front against his former club, with Christian Eriksen brought back in to try and increase the supply line to the penalty box.
On either side of the Dane on the flanks could be the pairing of Aaron Lennon (right wing) and Andros Townsend (left wing).
Lennon, back in his natural right midfield position, has been one of Spurs' better performers of late. Meanwhile, Townsend has impressed in cameos out left. Each has done good work attacking full-backs and getting crosses in and will be keen to start yielding more production from their efforts.
Wednesday could be the ideal opportunity to start both on their respective natural sides, helping to stretch West Ham and disrupt the discipline and shape that got the better of Spurs last time out.
Tottenham will be hoping this London derby is the perfect solution to the early winter blues currently enveloping the club. The possibility of a loss to West Ham making things even worse and dumping them out of the Capital One Cup would mean a pretty miserable Christmas is in the offing.
Predicted Tottenham lineup versus West Ham:
Brad Friedel; Kyle Walker, Younes Kaboul, Vlad Chiriches, Danny Rose; Aaron Lennon, Mousa Dembele, Lewis Holtby, Andros Townsend; Christian Eriksen; Jermain Defoe.